This invention relates to novel pyrrolesulfonamide derivatives. More specifically, this invention is concerned with pyrrolo[2,3-e][1,2]thiazine derivatives, pyrrolo[3,4-e][1,2]thiazine derivatives, pyrrolo[2,3-f][1,2]thiazepine derivatives and pyrrolo-[3,4-f][1,2]thiazepine derivatives, and salts thereof, said derivatives and salts having strong serotonin-2 receptor antagonistic action of excellent selectivity and being useful, for example, for the prevention or treatment of ischemic heart diseases such as angina pectoris, arrhythmia, myocardial infarction, congestive heart failure and post-PTCA restenosis, cerebrovascular disturbances such as cerebral infarction and cerebral sequelae after subarachnoid hemorrhage, peripheral circulatory disturbances such as arteriosclerosis obliterans, thromboangiitis obliterans and Raynaud disease, and hypertension; their preparation processes; and pharmaceuticals containing them as effective ingredients.
Serotonin is a compound contained abundantly in platelets, which are a blood component, and in a central nervous system, it acts as a neurotransmitter. In platelets, it is released upon stimulation by thromboxane A2, ADP, collagen or the like, and synergistically acts on release of various platelet aggregation factors through activation of serotonin-2 receptors in the platelets and vascular smooth muscle cells and also on vasoconstriction by norepinephrine through xcex11 receptors, thereby inducing strong platelet aggregation and vasoconstriction [P. M. Vanhoutte, xe2x80x9cJournal of Cardiovascular Pharmacologyxe2x80x9d, Vol. 17 (Supple. 5), S6-S12 (1991)].
Serotonin is also known to potentiate proliferation of vascular smooth muscle cells [S. Araki et al., xe2x80x9cAtherosclerosisxe2x80x9d, Vol. 83, pp.29-34(1990)]. It has been considered that, particularly when endothelial cells are injured as in arteriosclerosis or myocardial infarction, the vasoconstricting action and thrombus forming action of serotonin are exasperated, thereby reducing or even stopping blood supply to myocardial, cerebral and peripheral organs [P. Golino et al., xe2x80x9cThe New England Journal of Medicinexe2x80x9d, Vol. 324, No. 10, pp.641-648(1991), Y. Takiguchi et al., xe2x80x9cThrombosis and Haemostasisxe2x80x9d, Vol. 68(4), pp.460-463(1992), A. S. Weyrich et al., xe2x80x9cAmerican Journal of Physiologyxe2x80x9d, Vol. 263, H349-H358(1992)]. Being attracted by such actions of serotonin or serotonin-2 receptors, various attempts are now under way to use a serotonin-2 receptor antagonist as a pharmaceutical for ischemic diseases of the heart, the brain and peripheral tissues.
Several compounds, led by sarpogrelate, are known to have serotonin-2 receptor antagonistic action. They however do not include anything having the pyrrolo[2,3-e][1,2]thiazine skeleton, pyrrolo[3,4-e][1,2]thiazine skeleton, pyrrolo[2,3-f][1,2]thiazepine skeleton or pyrrolo[3,4-f][1,2]thiazepine skeleton. Those known to have serotonin-2 receptor antagonistic action are accompanied with many problems to be improved in potency, toxicity, side effects or the like. On the other hand, medicines which have anti-serotonin action and xcex11-blocking action in combination are considered to become extremely effective medicines for the treatment and prevention of hypertension and ischemic heart diseases, because they have possibility to reduce side effects, such as orthostatic hypotension and reflex tachycardia, induced by antihypertensive action on the basis of the xcex11-blocking action and hypertension is a serious risk factor for ischemic heart diseases.
In view of the foregoing circumstances, the present inventors have proceeded with extensive research toward compounds which have strong serotonin-2 receptor antagonistic action and low toxicity and less side effects and are useful for the treatment and prevention of ischemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances. As a result, it has been found that pyrrolesulfonamides represented by the below-described formula (I) meet the above conditions. It has also been found that the compounds according to the present invention include those also having xcex11-blocking action in combination and that such compounds are useful as antihypertensives or the like having less side effects and are widely usable for the treatment and prevention of circulatory diseases.
The present invention has been completed based on the above described findings. A first object of the present invention is to provide a pyrrolesulfonamide derivative or a salt thereof, said pyrrolesulfonamide derivative being represented by the following formula (I): 
wherein
the ring P represented by 
xe2x80x83means a pyrrole ring represented by the following structure: 
xe2x80x83in which R represents an alkyl group, a cycloalkyl group, a cycloalkyl-alkyl group or a substituted or unsubstituted aralkyl group;
the dashed line indicates the presence or absence of a bond; and, when the bond indicated by the dashed line is present, Z2 is not present and Z1 represents a hydrogen atom but, when the bond indicated by the dashed line is absent, Z1 represents a hydrogen atom and Z2 represents a hydroxyl group; or Z1 and Z2 are combined together to represent an oxygen atom or a group NOR1 in which R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryl group;
l represents 0 or 1;
A represents a substituted or unsubstituted alkylene group, a substituted or unsubstituted alkenylene group or a substituted or unsubstituted alkynylene group; and
Y represents a group 
xe2x80x83in which W represents CH, Cxe2x95x90 or a nitrogen atom; and, when W represents CH, m stands for 0 or 1, B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group, a group xe2x80x94C(OH)R2xe2x80x94 in which R2 represents a substituted or unsubstituted aryl group, a group xe2x80x94CHR3xe2x80x94 in which R3 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted cyclic or acyclic acetal group; when W represents Cxe2x95x90, m stands for 1, B represents a group 
xe2x80x83in which the double bond is coupled with W and R4 represents a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; when W represents a nitrogen atom, m stands for 0 or 1, and B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group or a group xe2x80x94CHR5xe2x80x94 in which R5 represents a substituted or unsubstituted aryl group; E1 and E2 each independently represents a hydrogen atom or a lower alkyl group; and D represents a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted aromatic heterocyclic group.
Another object of the present invention is to provide a preparation process of the pyrrolesulfonamide derivative (I) or its salt.
A further object of the present invention is to provide a pharmaceutical which comprises the pyrrolesulfonamide derivative (I) or its pharmaceutically-acceptable salt as an effective ingredient and is usable for the treatment or the like of circulatory diseases.
In the pyrrolesulfonamide derivatives (I) of the present invention, the ring P represents one of the following pyrrole rings: 
wherein R has the same meaning as defined above.
Preferred examples of the group R bonded to the nitrogen atom of the pyrrole ring can include linear or branched alkyl groups having 1-8 carbon atoms preferably, such as methyl, ethyl, n-propyl, isopropyl and n-pentyl; cycloalkyl groups having 3-8 carbon atoms, such as cyclopropyl, cyclopentyl and cyclohexyl; cycloalkylalkyl groups having 4-8 carbon atoms, such as cyclopropylmethyl, cyclohexylmethyl and cyclohexylethyl; and aralkyl groups having 7-22 carbon atoms, such as diphenylmethyl, benzyl and phenethyl. For example, one or more hydrogen atoms of each of these groups may be substituted by a like number of halogen atoms such as fluorine, chlorine and/or bromine atoms, alkyl groups having 1-4 carbon atoms preferably, such as methyl and/or ethyl, and/or alkoxy groups having 1-4 carbon atoms preferably, such as methoxy and/or ethoxy. Among these, particularly preferred are methyl and ethyl.
Further, l stands for 0 or 1 in the compound (I) according to the present invention. As the combination between the ring P and l, preferred examples can be (A) and 1, (A) and 0, and (B) and 1. Of these, the combinations of (A) and 1 and (A) and 0 are particularly preferred.
On the other hand, preferred examples of the group A in the compound (I) according to the present invention can include linear or branched alkylene groups having 2-10 carbon atoms, such as ethylene, trimethylene, tetramethylene, pentamethylene and octamethylene; linear or branched alkenylene groups having 4-10 carbon atoms, such as 2-butenylene and 3-pentenylene; and linear or branched alkynylene groups having 4-10 carbon atoms, such as 2-butynylene and 3-pentynylene. One or more of the hydrogen atoms of each of these groups may be substituted by a like number of halogen atoms such as fluorine, chlorine and/or bromine atoms. Among the above groups, trimethylene and tetramethylene are particularly preferred.
Further, preferred examples of the group Z1 and the group Z2 in the compound (I) according to the present invention can include the following combinations: when the bond indicated by the dashed line is present, Z2 is not present and Z1 represents a hydrogen atom; when the bond indicated by the dashed line is absent, Z1 represents a hydrogen atom and Z2 represents a hydroxyl group, or Z1 and Z2 are combined together to represent an oxygen atom or the group NOR1.
Preferred examples of R1 in the group NOR1 can include a hydrogen atom; linear or branched alkyl groups having 1-4 carbon atoms preferably, such as methyl and ethyl; aryl groups having 6-14 carbon atoms, such as phenyl and naphthyl; and aralkyl groups having 7-22 carbon atoms, such as benzyl and phenethyl. One or more of the hydrogen atoms of each of these groups may be substituted by a like number of halogen atoms such as fluorine, chlorine and/or bromine atoms, alkyl groups having 1-4 carbon atoms preferably, such as methyl and/or ethyl, and/or alkoxy groups having 1-4 carbon atoms preferably, such as methoxy and/or ethoxy. Of these, hydrogen atom and methyl group are particularly preferred.
In the compound (I) according to the present invention, Y is a group 
wherein B, D, E1, E2, W and m have the same meanings as defined above. The group represented by the following formula: 
wherein E1, E2 and W have the same meanings as defined above is a heterocyclic group derived from piperidine or piperazine, and two or less of the hydrogen atoms on the ring may be substituted by a like number of alkyl groups having 1-4 carbon atoms preferably, such as methyl and/or ethyl.
When the above group is a heterocyclic group derived from piperidine, m stands for 0 or 1 (with the proviso that m stands for 1 when W represents Cxe2x95x90), and B represents a carbonyl group, a sulfonyl group, an alkylene group (an alkylene group having 1-4 carbon atoms preferably, with a methylene group being particularly preferred), an alkenylene group (an alkenylene group having 2-5 carbon atoms preferably, with a 2-propenylene group being particularly preferred), a group xe2x80x94C(OH)R2xe2x80x94 in which R2 is an aryl group having 6-14 carbon atoms, such as phenyl or naphthyl, in which one or more of the hydrogen atoms may be substituted, a group xe2x80x94CHR3xe2x80x94 in which R3 is an aryl group having 6-14 carbon atoms, such as phenyl or naphthyl, in which one or more of the hydrogen atoms may be substituted, a group 
in which the double bond is coupled with W, R4 represents an aryl group having 6-14 carbon atoms, such as phenyl or naphthyl, or an aralkyl group having 7-22 carbon atoms, such as benzyl or phenethyl, and these groups may be in substituted forms, or a cyclic or acyclic acetal group in which one or more of the hydrogen atoms may be substituted.
Exemplary cyclic or acyclic acetal groups include: 
In the above-described definition of B, preferred examples of substituents on the groups R2, R3 and R4 can include one or more alkyl groups having 1-4 carbon atoms, such as methyl and ethyl; aryl groups having 6-14 carbon atoms, such as phenyl and naphthyl; halogen atoms such as fluorine atoms, chlorine atoms and bromine atoms; alkoxy groups having 1-4 carbon atoms, such as methoxy and ethoxy; hydroxyl groups; cyano groups; and nitro groups.
Further, illustrative of substituents on the cyclic or acyclic acetal are halogen atoms such as fluorine atoms, chlorine atoms, and bromine atoms; alkyl groups having 1-4 carbon atoms, such as methyl and ethyl; aryl groups having 6-14 carbon atoms, such as phenyl and naphthyl; aralkyl groups having 7-22 carbon atoms, such as benzyl and phenethyl; and alkylidene groups having 1-4 carbon atoms preferably, such as methylidene and ethylidene.
As a particularly preferred example of B, a carbonyl group can be mentioned.
When the heterocyclic group is a group derived from piperazine, m stands for 0 or 1 (preferably 0), and B represents a carbonyl group, a sulfonyl group, an alkylene group (preferably, an alkylene group having 1-4 carbon atoms, with a methylene group being particularly preferred), an alkenylene group (preferably, an alkenylene group having 3-6 carbon atoms, with a 2-propenylene group being particularly preferred), a group xe2x80x94CHR5xe2x80x94 in which R5 represents an aryl group having 6-14 carbon atoms, such as phenyl or naphthyl.
The above-described R5 may be substituted further, for example, by one or more of halogen atoms such as fluorine, chlorine and/or bromine, alkyl groups having 1-4 carbon atoms preferably, such as methyl and/or ethyl, alkoxy groups having 1-4 carbon atoms preferably, such as methoxy and/or ethoxy, hydroxyl groups, and/or the like.
As a preferred example of the above-described B, a substituted or unsubstituted phenylmethylene group can be mentioned.
Preferred examples of group D can include aromatic hydrocarbon groups having 6-28 carbon atoms preferably, such as a phenyl group in which one or more of the hydrogen atoms may be substituted and a naphthyl group in which one or more of the hydrogen atoms may be substituted.
Other preferred examples of D can include aromatic heterocyclic groups, preferably those each of which is monocyclic or bicyclic and contains three or less hetero atoms, such as pyridyl, pyrimidinyl, benzisothiazolyl, benzisoxazolyl, indazolyl and indolyl groups in which one or more of hydrogen atoms may be substituted. Examples of the hetero atoms can include oxygen, sulfur and nitrogen atoms.
Examples of the substituents for the above aromatic hydrocarbon group or aromatic heterocyclic group can include halogen atoms such as fluorine, chlorine and bromine; alkyl groups having 1-4 carbon atoms preferably, such as methyl and ethyl; alkoxyl groups having 1-4 carbon atoms preferably, such as methoxy and ethoxy; aryl groups having 6-14 carbon atoms, such as phenyl and naphthyl; aralkyl groups having 7-22 carbon atoms, such as benzyl and phenethyl; aralkyloxy groups having 7-22 carbon atoms preferably, such as benzyloxy; cyano groups; nitro groups; carboxyl groups; alkoxycarbonyl groups (with an alcohol moiety thereof having 1-6 carbon atoms preferably); lower alkylsulfonylamino groups (with an alkyl moiety thereof having 1-4 carbon atoms preferably); carbamoyl groups; and hydroxyl groups.
Among these examples of group D, preferred ones can include phenyl groups which may be unsubstituted or substituted by one or more of halogen atoms, alkoxy groups and/or hydroxyl groups; benzisothiazolyl groups which may be unsubstituted or substituted by one or more halogen atoms; benzisoxazolyl groups which may be unsubstituted or substituted by one or more halogen atoms; and indazolyl groups which may be unsubstituted or substituted by one or more halogen atoms. Particularly preferred are an unsubstituted phenyl group; and phenyl groups substituted by one or more of fluorine atoms, methoxy groups and/or hydroxyl groups.
Many of the compounds (I) according to the present invention have isomers. It is to be noted that these isomers and mixtures thereof are all embraced by the present invention.
The pyrrolesulfonamide derivatives (I) according to the present invention can be prepared by various processes. It is however preferred to prepare each of them, for example, by using a pyrrolesulfonamide derivative (IIa) or (IIaxe2x80x2), which is available by Process 1 to be described below, and following any one of the processes to be described as Process 2 onwards.
Process 1
Pyrrolesulfonamide derivatives (IIa) and (IIaxe2x80x2) useful as starting materials can be synthesized, for example, by the following process:
Process (a)
Compounds represented by the formula (IIa) and (IIaxe2x80x2) can be obtained in accordance with the following reaction scheme, namely, by converting a 1-substituted pyrrole-3-sulfonic acid represented by the formula (XII) or a salt thereof into a 1-substituted pyrrole-3-sulfonyl halide represented by the formula (XIII), reacting glycine, xcex2-alanine or a derivative thereof represented by the formula (XIV) or an organic or inorganic acid salt thereof with the compound (XIII) and, if necessary, conducting deprotection to obtain a compound represented by the formula (XV) and then subjecting the thus-obtained compound to a ring-closing reaction. 
wherein M represents a hydrogen ion, an alkali metal ion, an alkaline earth metal ion or a quaternary ammonium ion, p stands for 1 when M represents a hydrogen ion, an alkali metal ion or a quaternary ammonium ion or p stands for 2 when M represents an alkaline earth metal ion, q stands for 0 or 1, R6 represents a hydrogen atom or a carboxyl-protecting group, Xxe2x80x3 represents a chlorine atom or a bromine atom, and R and l have the same meanings as defined above.
Illustrative of M in the compound represented by the formula (XII) in the above scheme are hydrogen ion; alkali metal ions such as sodium ion and potassium ion; alkaline earth metal ions such as barium ion; and quaternary ammonium ions such as pyridinium ion. As representative preparation processes of the compound represented by the formula (XII), the following two processes can be mentioned.
[Preparation process of the compound (XII)xe2x80x941]
The compound represented by the formula (XII) can be obtained in accordance with the following formula, namely, by causing a sulfonating agent such as sulfur trioxide-pyridine complex to act on a 1-substituted pyrrole (XVIII) and, if necessary, treating the resultant compound with an acid such as hydrochloric acid or sulfuric acid or a base such as sodium hydroxide, sodium carbonate, sodium hydrogencarbonate or barium hydroxide. 
wherein M, R, p and q have the same meanings as defined above.
[Preparation process of the compound (XII)xe2x80x942]
The compound represented by the formula (XII) can be obtained in accordance with the following formula, namely, by causing trimethylsilyl chlorosulfonate (XIX) to act on a 1-substituted-2-tri-n-butylstannylpyrrole represented by the formula (XVII) in a solvent, which does not take part in the reaction, such as carbon tetrachloride or 1,2-dichloroethane and then hydrolyzing the resultant compound. Here, a basic substance may be allowed to exist concurrently, whereby the reaction product can be obtained as a salt. 
wherein M, R, p and q have the same meanings as defined above.
Further, the compound (XIII) can be obtained by causing phosphorus pentachloride or phosphorus pentabromide to act on the compound (XII) in a solvent which does not take part in the reaction, such as ethyl ether or toluene.
In addition, as the carboxyl-protecting group represented by the group R6 in the compound (XIV), it is possible to use, in addition to lower alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and t-butyl and aralkyl groups having 7-20 carbon atoms, such as benzyl and 9-anthrylmethyl, conventional protecting groups such as those described in T. W. Greene: xe2x80x9cProtective Groups in Organic Synthesisxe2x80x9d (John Wiley and Sons, Inc.) and the like.
Further, as an illustrative synthesis process of the compound (XV), a process can be mentioned in which a base is added to the compound (XIII), as needed, and glycine, xcex2-alanine or a derivative thereof or an organic or inorganic acid salt thereof is caused to act. Usable examples of the base can include organic bases such as triethylamine and pyridine, and inorganic bases such as sodium hydrogencarbonate, potassium carbonate and sodium hydroxide.
The compound (XV) so obtained is subjected to a cyclizing reaction, optionally after removing the protecting group by virtue of a suitable method such as the action of an acid or a base, or catalytic reduction. This cyclizing reaction is conducted by treating the compound (XV) together with an organic acid such as methanesulfonic acid, an inorganic acid such as sulfuric acid or polyphosphoric acid or a mixture of such an organic or inorganic acid and phosphorus pentoxide at room temperature to 170xc2x0 C., preferably at 80-120xc2x0 C.
In this case, a solvent which does not take part in the reaction may be added as needed.
Further, the cyclizing reaction can also be practiced by, optionally after addition of a catalyst such as dimethylformamide to the compound (XV) in which R6 is a hydrogen atom, treating the compound with oxalyl chloride, thionyl chloride, thionyl bromide, oxalyl bromide, phosgene, phosphorus trichloride, phosphorus tribromide, phosphoryl chloride, phosphoryl bromide or the like to convert it into its corresponding acid halide and then treating the acid halide at xe2x88x9220xc2x0 C. to reflux temperature in the presence of a Lewis acid such as aluminum chloride, aluminum bromide, boron trifluoride-ether complex or tin tetrachloride in a solvent such as dichloromethane, 1,2-dichloroethane or nitromethane. In the above-described reactions, the compound (IIa) and the compound (IIaxe2x80x2) can be formed at varied ratios by changing the reaction conditions.
Process (b)
Compounds represented by the formula (IIb) and (IIbxe2x80x2) can be obtained in accordance with the following reaction scheme, namely, by converting a pyrrole-3-sulfonic acid represented by the formula (XX) or a salt thereof into a pyrrole-3-sulfonyl halide represented by the formula (XXI), reacting glycine, xcex2-alanine or a derivative thereof represented by the formula (XIV) or an organic or inorganic acid salt thereof with the compound (XXI) and, if necessary, conducting deprotection to obtain a compound represented by the formula (XXII) and then subjecting the thus-obtained compound to a ring-closing reaction. The compound (IIa) and compound (IIaxe2x80x2) can then be obtained by introducing groups R to the pyrrole-nitrogen atoms of the compounds (IIb),(IIbxe2x80x2), respectively. 
wherein Xxe2x80x2xe2x80x3 represents an eliminative group, and M, R, R6, Xxe2x80x3, l and p have the same meanings as defined above.
In the above scheme, the compound represented by the formula (XX) can be synthesized from pyrrole as a starting material by following the preparation process of the compound (XII)xe2x80x941 under Process (a) of Process 1. Further, the conversion of the compound (XX) into the compound (IIb) and the compound (IIbxe2x80x2) can be effected in a similar manner as in the conversion of the compound (XII) into the compound (IIa) and the compound (IIaxe2x80x2) in Process (a) of Process 1.
The conversion from the compound (IIb) into the compound (IIa) can be effected by treating the compound (IIb) with an organic or inorganic base and then reacting the compound represented by the formula (XVIa) or (XVIb), or by causing the compound (XVIa) or the compound (XVIb) to act on the compound (IIb) in the presence of such a base.
Examples of the eliminative group represented by the group Xxe2x80x2xe2x80x3 in the compound (XVIa) can include halogen atoms such as chlorine, bromine and iodine, alkylsulfonyloxy groups such as methanesulfonyloxy, and arylsulfonyloxy groups such as p-toluenesulfonyloxy. Exemplary organic or inorganic bases can include potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium hydride, triethylamine, sodium methoxide, and potassium t-butoxide. Further, illustrative solvents usable in the above reaction include acetone, 2-butanone, acetonitrile, tetrahydrofuran, dioxane, dimethylformamide, and dimethylsulfoxide. The reaction is conducted at xe2x88x9220xc2x0 C. to reflux temperature.
On the other hand, the conversion from the compound (IIbxe2x80x2) into the compound (IIaxe2x80x2) can also be effected under the same conditions as in the above-described conversion from the compound (IIb) into the compound (IIa).
Process 2
Among the pyrrolesulfonamide derivatives (I), compounds (Ia) in each of which Z1 and Z2 are combined together to represent an oxygen atom can be synthesized, for example, by any one of the following processes.
Process (a)
Each compound (Ia) can be obtained in accordance with the following reaction scheme, namely, by reacting a compound represented by the formula (II) with a compound represented by the formula (III) to convert the compound (II) into a compound represented by the formula (IV) and then reacting a nitrogen-containing compound represented by the formula (V) or a salt thereof with the compound (IV). 
wherein X and Xxe2x80x2 represent the same or different eliminative groups, and A, the ring P, Y and l have the same meanings as defined above.
In the above-described reaction, the conversion from the compound (II) into the compound (IV) can be effected by treating the compound (II) with an organic or inorganic base and then reacting the compound (III) with the compound (II), or by causing the compound (III) to act on the compound (II) in the presence of such a base.
The groups X and Xxe2x80x2 in the compound (III) are eliminative groups. Illustrative can be halogen atoms such as chlorine and bromine, alkylsulfonyloxy groups such as methanesulfonyloxy, and arylsulfonyloxy groups such as p-toluenesulfonyloxy.
Exemplary inorganic bases or organic bases can include sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, triethylamine, sodium ethoxide, sodium bis(trimethylsilyl)amide, and potassium t-butoxide. The reaction can be conducted at xe2x88x9278xc2x0 C. to reflux temperature in a solvent which does not take part in the reaction.
To prepare the compound (Ia) from the thus-obtained compound (IV) and the nitrogen-containing compound (V), it is only necessary to react the nitrogen-containing compound (V) or an organic acid salt or inorganic acid salt thereof with the compound (IV), optionally together with an organic base such as triethylamine, pyridine, collidine or potassium t-butoxide or an inorganic base such as potassium carbonate, sodium carbonate, sodium hydrogencarbonate, sodium hydroxide or sodium hydride and optionally with the addition of an alkali iodide such as potassium iodide or sodium iodide, in a solventless manner or in a solvent such as acetone, 2-butanone, acetonitrile, dimethylformamide, methanol, ethanol or the like at room temperature to 150xc2x0 C.
Examples of the nitrogen-containing compound (V) can include 1-phenylpiperazine, 1-(2-fluorophenyl)piperazine, 1-(3-fluorophenyl)piperazine, 1-(4-fluorophenyl)piperazine, 1-(4-hydroxyphenyl)piperazine, 1-(2-chlorophenyl)piperazine, 1-(3-chlorophenyl)piperazine, 1-(4-chlorophenyl)piperazine, 1-(2-methoxyphenyl)piperazine, 1-(3-methoxyphenyl)piperazine, 1-(4-methoxyphenyl)piperazine, 1-(4-methanesulfonamidophenyl)piperazine, 1-(4-cyanophenyl)piperazine, 1-(4-carbamoylphenyl)piperazine, 1-(4-methoxycarbonylphenyl)piperazine, 1-(2-pyridyl)piperazine, 1-(2-pyrimidinyl)piperazine, 1-benzylpiperazine, 1-diphenylmethylpiperazine, 1-cinnamylpiperazine, 1-benzoylpiperazine, 1-(4-benzyloxybenzoyl)piperazine, 1-(4-hydroxybenzoyl)piperazine, 1-(2-furoyl)piperazine, 1-(1,2-benzisoxazol-3-yl)piperazine, 4-phenylpiperidine, 4-benzylpiperidine, xcex1,xcex1-bis(4-fluorophenyl)-4-piperidinemethanol, 4-(4-fluorobenzoyl)piperidine, 4-benzoylpiperidine, 4-(4-methoxybenzoyl)piperidine, 4-(4-chlorobenzoyl)piperidine, 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine, 4-(6-fluoro-1H-indazol-3-yl)piperidine, 4-[(4-fluorophenyl)sulfonyl]piperidine, 4-[bis(4-fluorophenyl)methylene]piperidine, and 4-(4-fluorobenzoyl)piperidine ethylene acetal.
These compounds are either known in the art or readily available by processes known per se in the art or by processes similar to such known processes.
Process (b)
Further, the compound (Ia) can also be obtained by causing a nitrogen-containing compound represented by the formula (VI) to act on the compound represented by the formula (II) in accordance with the following reaction formula: 
wherein A, the ring P, X, Y and l have the same meanings as defined above.
The conversion from the compound (II) into the compound (Ia) is conducted by causing the compound (VI) to act either after treatment of the compound (II) with an inorganic base or an organic base or in the presence of an inorganic base or an organic base. Reaction conditions are similar to those employed upon conversion from the compound (II) into the compound (IV) and described above under Process (a) of Process 2. Further, the compound (VI) can be synthesized by reacting the compound (III) with the compound (V) in a manner known per se in the art.
Process 3
Among the pyrrolesulfonamide derivatives (I), the compounds (Ic) and (Ie) in each of which Z1 and Z2 are combined together to represent a group NOR1 can each be synthesized by any one of the following processes.
Process (a)
Each compound (Ie) is obtained in accordance with the following reaction scheme, namely, by causing hydroxylamine or a derivative thereof (VII) or a salt thereof to act on a compound represented by the formula (IV) and then causing a nitrogen-containing compound (V) to act. 
wherein A, the ring P, R1, X, Y and l have the same meanings as defined above.
The reaction between the compound (IV) and the hydroxylamine or its derivative (VII) is effected, if necessary, in the presence of an organic base such as pyridine, triethylamine, collidine or sodium acetate or an inorganic base such as potassium carbonate or sodium hydroxide. The hydroxylamine or its derivative (VII) may also be used in the form of an organic acid salt or an inorganic acid salt.
The reaction is conducted at 0xc2x0 C. to reflux temperature, preferably 0xc2x0 C.-100xc2x0 C. by using a suitable solvent, for example, methanol, ethanol, propanol, tetrahydrofuran, dimethylformamide or dimethylsulfoxide as needed.
Further, the conversion from the thus-obtained compound (VIII) into the compound (Ie) can be effected under similar conditions as in the conversion from the compound (IV) into the compound (Ia) shown above under Process (a) of Process 2.
Process (b)
Each compound (Ic) is obtained by causing hydroxylamine or its derivative (VII) or a salt thereof to act on a compound (Ib) in accordance with the following reaction formula. 
wherein A, the ring P, R1 and l have the same meanings as defined above, and Yxe2x80x2 represents a group 
xe2x80x83in which when W represents CH, Bxe2x80x2 represents a sulfonyl group, an alkylene group, an alkenylene group, a group xe2x80x94C(OH)R2xe2x80x94 in which R2 represents a substituted or unsubstituted aryl group, a group xe2x80x94CHR3xe2x80x94 in which R3 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted cyclic or acyclic acetal group; when W represents Cxe2x95x90, Bxe2x80x2 represents a group 
xe2x80x83in which the double bond is coupled with W and R4 represents a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; when W represents a nitrogen atom, Bxe2x80x2 represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group or a group xe2x80x94CHR5xe2x80x94 in which R5 represents a substituted or unsubstituted aryl group; and D, E1, E2 and m have the same meanings as defined above.
The conversion from the compound (Ib) into the compound (Ic) can be effected under similar conditions as the conversion from the compound (IV) into the compound (VIII) shown above under Process (a) of Process 3.
Process 4
Among the pyrrolesulfonamide derivatives (I), the compounds (Id) and (If) in each of which Z1 represents a hydrogen atom and Z2 represents a hydroxyl group can each be synthesized by any one of the following processes.
Process (a)
Each compound (If) is obtained in accordance with the following reaction scheme, namely, by reducing a compound represented by the formula (IV) and then causing a nitrogen-containing compound (V) to act. 
wherein A, the ring P, X, Y and l have the same meanings as defined above.
The conversion from the compound (IV) into the compound (IX) is conducted by treating the compound represented by the formula (IV) with a reducing agent such as sodium borohydride, potassium borohydride or sodium cyanoborohydride at xe2x88x9278xc2x0 C. to reflux temperature, preferably xe2x88x9220xc2x0 C. to room temperature in a conventionally used solvent.
The conversion from the compound (IX) into the compound (If) can be effected under similar conditions as the conversion from the compound (IV) into the compound (Ia) shown above under Process (a) of Process 2.
Process (b)
Each compound (Id) is obtained by reducing a compound represented by the formula (Ib) in accordance with the following reaction formula. 
wherein A, the ring P, Yxe2x80x2 and l have the same meanings as defined above.
The conversion from the compound (Ib) into the compound (Id) can be effected under similar conditions as in the conversion from the compound (IV) into the compound (IX) shown above under Process (a) of Process 4.
Process 5
Among the pyrrolesulfonamide derivatives (I), the compounds (Ig) in each of which the bond indicated by the dashed line is present and Z1 represents a hydrogen atom can be synthesized by any one of the following processes.
Process (a)
Each compound (Ig) is obtained in accordance with the following reaction scheme, namely, by subjecting a compound represented by the formula (IX) to a dehydration reaction to obtain a compound represented by the formula (X) and then causing a nitrogen-containing compound (V) to act on the compound (X). 
wherein A, the ring P, X, Y and l have the same meanings as defined above.
In the above-described reaction, the conversion from the compound (IX) into the compound (X) can be effected by treating the compound (IX) with an acid such as hydrogen chloride, hydrogen bromide, sulfuric acid, methanesulfonic acid or p-toluenesulfonic acid at xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably at xe2x88x9220xc2x0 C. to room temperature in a solvent such as water, methanol, ethanol, ethyl acetate, chloroform or toluene.
As an alternative, the conversion into the compound (X) can also be effected by causing methanesulfonyl chloride, p-toluenesulfonyl chloride, phosphorus trichloride, phosphorus oxychloride, thionyl chloride or the like and a base such as triethylamine, pyridine or collidine to act on the compound (IX), if necessary, in a solvent such as dichloromethane, chloroform or toluene.
The conversion from the compound (X) into the compound (Ig) can be effected under similar conditions as in the conversion from the compound (IV) into the compound (Ia) described above under Process (a) of Process 2.
Process (b)
Each compound (Ig) is obtained by subjecting a compound represented by the formula (If) to a dehydration reaction in accordance with the following reaction formula: 
wherein A, the ring P, Y and l have the same meanings as defined above.
In the above-described reaction, the conversion from the compound (If) into the compound (Ig) can be effected under similar conditions as in the conversion from the compound (IX) into the compound (X) described above under Process (a) of Process 5.
If necessary, the compounds (I) of the present invention obtained according to the above-described processes can each be reacted with one of various acids to convert the compound into its salt. Then, the resulting salt can be purified by a method such as recrystallization or column chromatography.
Exemplary acids usable for the conversion of the pyrrolesulfonamide derivatives (I) into their salts can include inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid and hydrobromic acid; and organic acids such as maleic acid, fumaric acid, tartaric acid, lactic acid, citric acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid, adipic acid, palmitic acid and tannic acid.
Further, the compounds (I) according to the present invention include those containing asymmetric centers. Each racemic mixture can be isolated by one or more of various methods, whereby a single optically-active substance can be obtained. Usable methods include, for example:
(1) Isolation by an optically active column.
(2) Isolation by recrystallization subsequent to conversion into a salt with an optically active acid.
(3) Isolation by an enzyme reaction.
(4) Isolation by a combination of the above methods (1) to (3).
The pyrrolesulfonamide derivatives (I) and their salts, which are obtained as described above, have strong serotonin-2 blocking action as will be demonstrated in tests to be described subsequently herein. Moreover, the compounds (I) according to the present invention have also been found to include those also having xcex11 blocking action. From the results of toxicity tests, the compounds (I) according to the present invention have also been found to possess high safety.
The compounds (I) according to the present invention can therefore be used as pharmaceuticals for the treatment of circulatory diseases such as ischemic heart diseases, cerebrovascular disturbances, peripheral circulatory disturbances and hypertension.
When the pyrrolesulfonamide derivatives (I) according to this invention are used as pharmaceuticals, they can be administered in an effective dose as they are. As an alternative, they can also be formulated into various preparation forms by known methods and then administered.
Exemplary preparation forms as medicines include orally administrable preparation forms such as tablets, powders, granules, capsules and syrups as well as parenterally administrable preparation forms such as injections and suppositories. Whichever preparation form is used, a known liquid or solid extender or carrier usable for the formulation of the preparation form can be employed.
Examples of such extender or carrier include polyvinylpyrrolidone, arabic gum, gelatin, sorbit, cyclodextrin, tragacanth gum, magnesium stearate, talc, polyethylene glycol, polyvinyl alcohol, silica, lactose, crystalline cellulose, sugar, starch, calcium phosphate, vegetable oil, carboxymethylcellulose, sodium laurylsulfate, water, ethanol, glycerin, mannitol, syrup, and the like.
When the compounds (I) according to the present invention are used as pharmaceuticals, their dose varies depending on the administration purpose, the age, body weight, conditions, etc. of the patient to be administered. In oral administration, the daily dose may generally be about 0.01-1,000 mg.
The present invention will next be described in further detail by the following referential examples, examples and tests. It is however to be noted that the present invention is by no means limited to the following examples.